The government has certain rights in this invention pursuant to research grant number NIDR RO1 DEO8223.
This invention relates generally to compositions of matter and, more particularly, to trans-beta-isocyanatoacrylate esters, their preparation, and polymers made from such esters. The polymers have utility, including as adhesives for living tissue and inanimate objects.
Certain .alpha.-substituted isocyanato esters and intermediates have previously been disclosed in U.S. Pat. Nos. 4,704,466 and 4,876,323. The esters disclosed in those patents were of the structure: ##STR2## where X and Y were selected from one of the following pairs: EQU X=CO.sub.2 C.sub.2 H.sub.5 and Y=Si(CH.sub.3).sub.3 ;
and EQU X=CO and Y=none
and R was selected from C.sub.20 or lower, linear or branched alkyls; aryl; alkaryl; aralkyl; halogenated alkyl (C.sub.20 or lower): halogenated aryl; alkoxyalkyl; and alkoxyaryl. The .alpha.-substituted isocyanato esters were disclosed to have utility in the preparation of adhesive compositions, such as for use in the joining of living tissue.
The present inventors have previously reported a process in which trans-beta-isocyanatoacrylate esters in solution were believed to have been prepared. Attempts to isolate and positively identify these esters were unsuccessful because they were unstable in the trans- configuration and readily isomerized to the cis-configuration. The cis- esters then readily cyclized to form N-carboxy-anhydride 1,3-oxazine-2,4(6H)-dione with loss of the isocyanate functionality. Although it was reported that the presence of an acid chloride impurity in the solution caused the trans- esters to be stabilized at room temperature, it was not felt that the esters would remain stable with the addition of heat for distillation purposes, particularly since it was well known that acids which are capable of forming anhydrides readily cyclize upon heating.
There have also been other reports of methods in which various beta-isocyanate-type compounds in solution were believed to have been produced. In each of these methods, however, the isocyanatoacrylate esters were not isolated from the solution. For example, Kircheldorf in Angrew, Chem. Internat. Edit Vol. 11, pages 128-129 (1972) prepared a beta-isocyanatocrotonic ester and showed that the isocyanate was present in the liquid phase. The isocyanate, however, was unstable and readily cyclized to 2-ethyl-1,3-oxazine-6-one.
Kircheldorf in Makromolekulare Chemie Vol. 173, pages 13-41 (1973) and Washburne et al. in J. Org. Chem. Vol. 37, pages 1938-42 (1972) have disclosed the preparation of beta-isocyanatoacrylic acids from maleic anhydride. The isocyanate intermediary was shown to be present but was destroyed during ring closing and was not isolated.
In Organic Reaction Vol. 3, page 342 (1946) the work of Curtius and Rodenhausen as originally reported in J. Prakt. Chem. Vol. 52, page 433 (1895) showed that isocyanates were prepared from fumaric acid but the free isocyanate was not isolated.